The aims of this research are to identify further the feedback loops that regulate hemopoiesis by exploitation of cell lines that we have isolated and carry in culture. The H-1 cell line produces GM-CSF, a labile inhibitor of granulopoiesis, and probably an inhibitor of PFU-E proliferation. The H-1 cell is derived from bone marrow cells in liquid Dexter culture and has the characteristics of an adventitial reticular cell. The MAC line produces CSF and in vivo indices a granulocytosis whereas H-1 line does not induce granulocytosis. We hope to confirm existence of BFU-E inhibitor and determine its effect in vivo and on bi-\and tripotent cells in vitro, isolate and characterize the BFU-E inhibitor. We further will investigate why the H-1 line does not produce a granulocytosis in vivo and MAC line does, although both produce GM-CSF. Earlier studies showed that an osteosarcoma increased CFU-S content of bone marrow. We will induce more osteosarcoma by 55FE and test for a pluricellpoietin and, if present, commence its isolation and characterization. Through the above and allied in vivo and in vitro studies, we will define feedback loops regulating hemopoiesis, an understanding of which is essential for pathogenesis of diseases of hemopoiesis and their control.